PDBsum entry 2bc4

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protein ligands metals Protein-protein interface(s) links
Immune system PDB id
Protein chains
188 a.a. *
191 a.a. *
_CL ×4
Waters ×420
* Residue conservation analysis
PDB id:
Name: Immune system
Title: Crystal structure of hla-dm
Structure: Hla class ii histocompatibility antigen, dm alpha chain. Chain: a, c. Synonym: mhc class ii antigen dma. Engineered: yes. Hla class ii histocompatibility antigen, dm beta chain. Chain: b, d. Synonym: mhc class ii antigen dmb.
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: hla-dma, dma, ring6. Expressed in: drosophila melanogaster. Expression_system_taxid: 7227. Gene: hla-dmb, dmb, ring7.
Biol. unit: Dimer (from PQS)
2.27Å     R-factor:   0.229     R-free:   0.268
Authors: M.J.Nicholson,B.Moradi,N.P.Seth,X.Xing,G.D.Cuny,R.L.Stein, K.W.Wucherpfennig
Key ref: M.J.Nicholson et al. (2006). Small molecules that enhance the catalytic efficiency of HLA-DM. J Immunol, 176, 4208-4220. PubMed id: 16547258
18-Oct-05     Release date:   23-May-06    
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Protein chains
Pfam   ArchSchema ?
P28067  (DMA_HUMAN) -  HLA class II histocompatibility antigen, DM alpha chain
261 a.a.
188 a.a.*
Protein chains
Pfam   ArchSchema ?
P28068  (DMB_HUMAN) -  HLA class II histocompatibility antigen, DM beta chain
263 a.a.
191 a.a.
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 2 residue positions (black crosses)

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     membrane   2 terms 
  Biological process     immune response   2 terms 


J Immunol 176:4208-4220 (2006)
PubMed id: 16547258  
Small molecules that enhance the catalytic efficiency of HLA-DM.
M.J.Nicholson, B.Moradi, N.P.Seth, X.Xing, G.D.Cuny, R.L.Stein, K.W.Wucherpfennig.
HLA-DM (DM) plays a critical role in Ag presentation to CD4 T cells by catalyzing the exchange of peptides bound to MHC class II molecules. Large lateral surfaces involved in the DM:HLA-DR (DR) interaction have been defined, but the mechanism of catalysis is not understood. In this study, we describe four small molecules that accelerate DM-catalyzed peptide exchange. Mechanistic studies demonstrate that these small molecules substantially enhance the catalytic efficiency of DM, indicating that they make the transition state of the DM:DR/peptide complex energetically more favorable. These compounds fall into two functional classes: two compounds are active only in the presence of DM, and binding data for one show a direct interaction with DM. The remaining two compounds have partial activity in the absence of DM, suggesting that they may act at the interface between DM and DR/peptide. A hydrophobic ridge in the DMbeta1 domain was implicated in the catalysis of peptide exchange because the activity of three of these enhancers was substantially reduced by point mutations in this area.

Literature references that cite this PDB file's key reference

  PubMed id Reference
23222639 A.I.Guce, S.E.Mortimer, T.Yoon, C.A.Painter, W.Jiang, E.D.Mellins, and L.J.Stern (2013).
HLA-DO acts as a substrate mimic to inhibit HLA-DM by a competitive mechanism.
  Nat Struct Mol Biol, 20, 90-98.
PDB code: 4i0p
21131964 A.K.Anders, M.J.Call, M.S.Schulze, K.D.Fowler, D.A.Schubert, N.P.Seth, E.J.Sundberg, and K.W.Wucherpfennig (2011).
HLA-DM captures partially empty HLA-DR molecules for catalyzed removal of peptide.
  Nat Immunol, 12, 54-61.  
21116684 Zaheer-ul-Haq, and W.Khan (2011).
Molecular and structural determinants of adamantyl susceptibility to HLA-DRs allelic variants: an in silico approach to understand the mechanism of MLEs.
  J Comput Aided Mol Des, 25, 81.  
20109023 N.P.Croft, and A.W.Purcell (2010).
Enhancing tumor vaccines: catalyzing MHC class II peptide exchange.
  Expert Rev Vaccines, 9, 129-132.  
19738910 K.Dickhaut, S.Hoepner, J.Eckhard, K.H.Wiesmueller, L.Schindler, G.Jung, K.Falk, and O.Roetzschke (2009).
Enhancement of tumour-specific immune responses in vivo by 'MHC loading-enhancer' (MLE).
  PLoS One, 4, e6811.  
19414787 M.J.Call, X.Xing, G.D.Cuny, N.P.Seth, D.M.Altmann, L.Fugger, M.Krogsgaard, R.L.Stein, and K.W.Wucherpfennig (2009).
In vivo enhancement of peptide display by MHC class II molecules with small molecule catalysts of peptide exchange.
  J Immunol, 182, 6342-6352.  
18767126 R.Yaneva, S.Springer, and M.Zacharias (2009).
Flexibility of the MHC class II peptide binding cleft in the bound, partially filled, and empty states: A molecular dynamics simulation study.
  Biopolymers, 91, 14-27.  
19005572 A.Ferrante, M.W.Anderson, C.S.Klug, and J.Gorski (2008).
HLA-DM mediates epitope selection by a "compare-exchange" mechanism when a potential peptide pool is available.
  PLoS ONE, 3, e3722.  
18343923 O.G.Goldstein, L.M.Hajiaghamohseni, S.Amria, K.Sundaram, S.V.Reddy, and A.Haque (2008).
Gamma-IFN-inducible-lysosomal thiol reductase modulates acidic proteases and HLA class II antigen processing in melanoma.
  Cancer Immunol Immunother, 57, 1461-1470.  
16947022 A.Haque, A.Das, L.M.Hajiaghamohseni, A.Younger, N.L.Banik, and S.K.Ray (2007).
Induction of apoptosis and immune response by all-trans retinoic acid plus interferon-gamma in human malignant glioblastoma T98G and U87MG cells.
  Cancer Immunol Immunother, 56, 615-625.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.